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Objective: To identify risk factors for stenosis and compare management strategies for stenosis etiology and to examine the efficacy of each approach. Patients with classic bladder exstrophy (CBE), a rare genitourinary malformation, may require construction of a continent urinary stoma (CUS) if incontinence persists. Stomal stenosis is a challenging complication as it is common, progressive, and recurrent., Methods: CBE patients who underwent CUS were retrospectively reviewed for risk factors for stenosis including stoma type, prior midline laparotomy number, and umbilicoplasty suture material. Stenosis etiology and management strategies were further reviewed., Results: A total of 260 CBE patients underwent CUS creation. Stenosis developed in 65 patients (25.0%) at a median interval of 1.9 years. Etiology included scar contracture (n = 41), keloid (n = 17), and hypertrophic scar (n = 7). Multifilament suture was the only variable associated with an increased risk of stenosis compared to monofilament suture (P = .009). Almost all patients required surgical intervention. Most scar contractures underwent stomal incision with success in 100%. Hypertrophic scars and keloids responded best to excision with local tissue rearrangement (66.7%). At last follow-up, all patients achieved success., Conclusion: Stomal stenosis is common and challenging for the reconstructive surgeon. Strategies to prevent and effectively manage this are greatly desired. Use of multifilament suture for the umbilicoplasty increased stenosis perhaps from a greater inflammatory response and scarring, while monofilament suture may reduce its incidence. Stomal incision for treating scar contractures, and excision with local tissue rearrangement for hypertrophic scars and keloids may improve successful primary surgical intervention., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To determine if the administration of standardized opioid disposal instructions with focused parental education improves proper disposal of leftover opioid medication among families of children undergoing ambulatory urologic surgery compared to routine postoperative instructions., Methods: A prospective, double-blinded, single-center randomized controlled trial was conducted in children 6-18 years undergoing ambulatory urology procedures between October 2021 and April 2023. Patients were randomized (1:1) to receive either the Food and Drug Administration (FDA) opioid disposal best practices worksheet plus nursing parental education or routine postoperative instructions alone. All patients were prescribed acetaminophen and ibuprofen and a per-protocol rescue opioid prescription. The primary outcome was rate of proper opioid disposal at 10-14 days post-procedure. Secondary outcomes included parents' postoperative pain measure (PPPM) scores, numerical pain scale (NPS) scores, and weight-based opioid utilization at 48 hours and 10-14 days., Results: We randomized 104 participants (53 intervention, 51 control) with 97% (101/104) complete follow-up data at 10-14 days. Patient demographics, procedural characteristics, and analgesia use were similar between groups. We observed no significant difference in proper opioid disposal rates between arms (31% intervention vs 18% control; estimated difference in proportion 13% [95% CI, -4%-29%]; P = .1). There were no increased odds of proper disposal of leftover opioid medication at 10-14 days with the intervention compared to the control (OR 2.0 [95% CI 0.8-5.1]; P = .1). We observed no differences in PPPM scores, NPS scores, or opioid utilization at 48 hours or 10-14 days., Conclusion: Providing formal opioid disposal instructions with parental education did not improve proper disposal of leftover opioid medication nor did it alter post-discharge opioid utilization after pediatric urologic surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To determine the rate of stone formation amongst patients of the exstrophy-epispadias complex with augmentation cystoplasty. We hypothesize that bowel segment choice influences the rate of stone formation after bladder augmentation and the rate of complications from bladder stone surgery., Methods: An IRB-approved institutional database of 1512 exstrophy-epispadias patients was reviewed retrospectively. Patients that had a history of bladder augmentation and were seen at our institution between 2003 and 2023 were included., Results: Out of 259 patients, bladder stones developed in 21.6% (56), of which the bowel segment used was colon in 147 patients and ileum in 100. Stones formed in 19% of colon augments compared to 29% ileal augments, however, this was not statistically significant (P = .07). The most common primary stone component was dahllite, followed by struvite for all augments (Table 1). The median time to stone treatment after augmentation was 4.14 years (0.75-31). Seventy-four percentage of patients had a recurrence that required a second surgery. The median time from first to second surgery and second to third surgery was 1.4 years and 2.22 years, respectively. Bladder stone surgery complications occurred in 14% of patients, vesicocutaneous fistula being the most common, and complications did not differ by augment type. Median follow-up after first stone intervention was 6.07 years (0-19.5)., Conclusion: The treatment of bladder stones in the exstrophy-epispadias complex remains challenging. Interventions to prevent recurrence are crucial as the majority of patients will require 2 or more stone surgeries in their lifetime., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To review the outcomes of classic bladder exstrophy (CBE) closure without the use of osteotomy or lower extremity/pelvic immobilization., Methods: A prospectively maintained institutional approved exstrophy-epispadias complex database of 1487 patients was reviewed for patients with CBE who had undergone closure without osteotomy nor immobilization. All patients were referred to the authors' institution for reconstruction later in life or for failed closure., Results: Of a total of 1016 CBE patients, 56 closure events were identified that met inclusion with a total of 47 unique patients. Thirty-eight closures were completed prior to 1990 (67.9%). Forty-five closure events developed eventual failure (45/56, 80.4%) (Table 1). Thirteen closure events were secondary closures (13/56, 23.2%). The primary closure failure rate was 83.7% (36/43) while the secondary closure failure rate was 69.2% (9/13). Failures were attributed to one or more of dehiscence, bladder prolapse, and vesicocutaneous fistula (25/45, 55.6%) (23/45, 51.1%) (6/45, 13.3%), respectively. Thirty-seven patients developed social continence (37/47, 78.7%), while only 8 patients developed spontaneous voided continence (7/47,17.0%) (Table 2). The most common methods of voiding were continent catheterizable channels (25/47, 53.2%) of which all were socially continent., Conclusion: These results illustrate the critical role osteotomy and postoperative immobilization can play in both primary and secondary exstrophy closure. While this is a historical case series, the authors believe that these results remain relevant to contemporary exstrophy surgeons., Competing Interests: Declaration of Competing Interest The authors have no financial or personal relationships with other people or organizations that could inappropriately influence their work., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Declaration of Competing Interest None Declared.

Objective: To test the hypothesis that phenotypes in bladder exstrophy result from alterations in detrusor smooth muscle cell (SMC) gene expression., Methods: We generated primary human bladder smooth muscle cell lines from patients with classic bladder exstrophy (CBE) undergoing newborn closure (n = 6), delayed primary closure (n = 5), augmentation cystoplasty (n = 6), and non-CBE controls (n = 3). Gene expression profiles were then created using RNA sequencing and characterized using gene set enrichment analysis (GSEA)., Results: We identified 308 differentially expressed genes in bladder exstrophy SMC when compared to controls, including 223 upregulated and 85 downregulated genes. Bladder exstrophy muscle cell lines from newborn closure and primary delayed closures shared expression changes in 159 genes. GSEA analysis revealed increased expression in the inflammatory response and alteration of genes for genitourinary development in newborn and delayed closure SMC. However, these changes were absent in SMC from older exstrophy patients after closure., Conclusion: Bladder exstrophy SMC demonstrate gene expression changes in the inflammatory response and genitourinary development. However, gene expression profiles normalized in exstrophy SMC from older patients after closure, suggesting a normalization of exstrophy SMC over time. Our in vitro findings regarding the normalization of exstrophy SMC gene expression following bladder closure suggest that the development of poor detrusor compliance in bladder exstrophy has a complex multifactorial etiology. Taken together, our findings suggest that alterations in SMC gene expression may explain abnormalities in the exstrophy bladder seen prior to and immediately after closure and suggest that surgical closure may allow exstrophy SMC to normalize over time., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To report the technique and outcomes of tissue expansion (TE) for generating additional penile skin for urethroplasty and/or skin coverage during primary or redo hypospadias repair in penoscrotal transposition (PST) patients with a proximal hypospadias., Methods: Proximal hypospadias and PST patients with a lack of penile skin, congenitally or after failed repair, who underwent TE assisted reconstruction were reviewed. TE were placed under the penile shaft and expanded skin was used for tubularized incised plate repair. Success was defined as urethral advancement to the corona or more distal with tension free skin coverage., Results: A total of 24 patients underwent reconstruction including 16 as part of primary repair and for redo repairs in 8. Nine patients experienced expander extrusion and posturethroplasty complications occurred in 43.8% of primary repairs and 75.0% of redo repairs; a urethrocutaneous fistula was most common (n = 8). Overall, success was achieved in 87.5% of patients with postoperative meatal locations almost all coronal (45.8%) or glanular (50.0%)., Conclusion: Proximal hypospadias reconstruction is challenging, and complications are not infrequent. TE is a useful alternative for complex patients with a skin paucity such that cutaneous coverage would be difficult following urethroplasty. Although the complication rate was 43.8% for primary repair, TE generated sufficient residual skin for success after additional reconstruction. For redo repair early use is most beneficial as there is more expandable skin. The pseudocapsules provide vascularized coverage to reinforce the urethra while there is sufficient skin to minimize the need for a skin graft for penile coverage., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate management trends in a single institution with a large referral population in classic bladder exstrophy (CBE) over the past twenty years., Methods: An institutional database of 1415 exstrophy-epispadias complex patients was retrospectively reviewed for CBE patients with primary closure between 2000 and 2019. Osteotomy, location of closure, age of closure, and outcome of closures were reviewed., Results: A total of 278 primary closures were identified, with 100 occurring at author's hospital (AH) and 178 at outside hospitals (OSH). Osteotomies were performed in 54% of cases at AH and 52.8% of cases at OSH. Osteotomy use increased over 20 years from 48.6% in 00's to 62.1% in 10's (P = .046). The total success rate at AH was 96% and 62.9% at OSH. The median age at primary closure at AH increased from 5 days (00's) to 20 days (10's), compared to the OSH which increased from 2 days (00's) to 3 days (10's)., Conclusion: Closure of CBE may be delayed for several reasons including insurance difficulties, transfer to another hospital, desire for second opinions, or surgeon preference. Delaying primary closure of bladder exstrophy gives families time to adjust lifestyle, arrange travel, and seek care at centers of excellence., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To describe long-term outcomes and experience with the tunica vaginalis flap (TVF) as a tissue augment for complex epispadias repair., Methods: A prospectively maintained institutional database was reviewed for patients who underwent epispadias repair with TVF from 2010 to 2021. Evaluation of patient characteristics between those who developed dehiscence or UCF and those who did not was performed via Mann-Whitney U, Kruskal-Wallis, or Fisher's exact test, as appropriate., Results: A total of 47 male patients were identified, of whom, 1 (2.1%) had cloacal exstrophy, 38 (80.9%) had classic bladder exstrophy or a variant, and 8 (17.0%) had epispadias as their primary exstrophy-epispadias complex diagnosis. The median age at epispadias repair was 13 months (IQR 11 - 19). The overall rate of fistula or dehiscence development was 19.1% (9 patients), of whom, 7 developed urethrocutaneous fistulae, 1 dehiscence, and 1 both. Notably, 0 of the 5 patients who had undergone prior epispadias repair and 0 of the 8 patients with a diagnosis of isolated epispadias developed a UCF or dehiscence after repair with TVF. Differences in age at repair, primary EEC diagnosis, prior epispadias repair, pre-repair testosterone, fibrin sealant utilization, closure layers, stent removal time, and bladder capacity at repair were not statistically significant (P>.05) CONCLUSION: Our expanded evaluation indicates that utilization of the tunica vaginalis as an adjunct to epispadias repair may provide durable protection against fistula development in EEC patients who have undergone prior epispadias repair and in primary repair of patients with isolated epispadias., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The exstrophy-epispadias complex is a rare congenital anomaly presenting as a wide spectrum of disorders. The complex nature of this malformation leads to continuous investigations of the basic science concepts behind it. Elucidating these concepts allows one to fully understand the mechanisms behind the disease in order to improve diagnosis, management, and treatment ultimately leading to improvement in patient quality of life. Multiple technological advancements within the last 10 years have been made allowing for new studies to be conducted. Herein, the authors conduct a literature review of studies from 2009 to 2019, considering novel theories regarding the genetics, embryology, bladder, bony pelvis, prostate, and genitalia of patients with bladder exstrophy-epispadias complex., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To explore a series of classic bladder exstrophy (CBE) cases referred to the authors' institution where primary closure with penile disassembly epispadias repair was complicated by penile injury. The penile disassembly technique is frequently combined with bladder closure in patients with CBE undergoing the complete primary repair of exstrophy (CPRE). Penile disassembly has been posited as a risk for penile injury by ischemic mechanisms., Methods: A prospectively-maintained institutional database of 1337 exstrophy-epispadias complex patients was reviewed for CPRE cases referred to the authors' institution, and those with injury to the penis were identified. The location, extent of injury, and subsequent management is reported., Results: One hundred and thirteen male CBE patients were referred after prior CPRE. Twenty-six (20%) were identified with penile loss and reviewed. Eighty-one percent were closed in the neonatal period, and 54% had a pelvic osteotomy. Median follow-up time was 9.9 years (range 0.6-21.3). Of 26 patients with penile loss, 77% had unilateral loss and in 23% had bilateral loss involving the glans and/or one or both corpora cavernosa. Three patients were successfully managed with myocutaneous neophalloplasty., Conclusion: Complete penile disassembly during bladder exstrophy closure may lead to penile injury. This major complication questions the continued application of complete penile disassembly in the reconstruction of bladder exstrophy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Posterior urethral valves (PUVs) present clinically across a varied spectrum, ranging from severe obstruction with massive distension of the bladder and upper urinary tracts in the fetus, to a much more indolent course with minor secondary changes in the young or older child. Type III (diaphragm) PUVs are relatively uncommon, and are associated with difficulty in passing a transurethral catheter into the bladder as well as smooth dilation of the bladder. The following case examines the unusual experiences of both diagnosing PUVs in a teenager, and capturing visual evidence of type III valves during cystourethroscopy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To describe the use of additional tissue recruited for coverage after penile lengthening in male exstrophy-epispadias complex patients using either local skin from tissue expansion (TE) or extragenital skin with a skin graft (SG) and report their respective outcomes., Methods: An institutionally approved database of exstrophy-epispadias complex patients was retrospectively reviewed for male patients who received penile reconstruction. This included a penile lengthening procedure and the subsequent use of TE and/or a full thickness skin graft to provide cutaneous coverage of gained corporal length., Results: A total of 50 patients (mean age 18.1 years) underwent penile reconstruction. TE was used in 27 patients, SG in 19, and 4 received a combination of TE and SG. The mean number of previous penile operations was 2.7 for patients that received TE and 3.1 for SG. A successful outcome from primary reconstruction was achieved in 35 patients (70%) and overall successful reconstruction was achieved by 48 patients (96%)., Conclusion: TE and SG are useful techniques in providing soft tissue coverage following penile lengthening. TE is the preferred technique for primary reconstruction in a lengthening procedure. When genital skin is not expandable or coverage from TE is insufficient after lengthening, extragenital skin (SG) is recruited., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To compare the surgical subspecialties performing bladder exstrophy closures and characterize their practice patterns using both a national and institutional database., Methods: The National Surgical Quality Improvement Program Pediatric (NSQIPP) database was reviewed for all bladder exstrophy closures performed from 2012 to 2017. A single institutional exstrophy-epispadias complex database of 1337 patients was reviewed for patients with a bladder closure at a referring institution from 1975 to 2018. Patients with cloacal exstrophy were excluded. The subspecialties of the surgeons performing the closures were identified. Practice patterns such as the use of a pelvic osteotomy and postoperative immobilization, and perioperative outcomes were compared for each subspecialty group., Results: A total of 84 bladder exstrophy patients from NSQIPP and 263 from the author's institutional database met the inclusion criteria. From NSQIPP, 88% of closures were performed by pediatric urologists while 12% were done by other subspecialists. From the institutional database, 75% of referred bladder exstrophy closures were done by a pediatric urologist, and 25% by other services. Gender, race, operation time, length of stay, and postoperative complications were not significantly different between the groups. In one database, pediatric surgeons performed closures earlier, and in another database, pediatric urologists had greater utilization of osteotomy with different immobilization techniques. Pediatric urologists had a higher success rate., Conclusion: Pediatric urologists performed the most bladder exstrophy closures in both databases; they operated on more delayed closures with a greater use of adjunctive procedures and a higher success rate. Differences in surgical training may contribute to the differences in practice patterns., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To investigate the diagnosis, surgical management, and outcomes in patients with variant EEC. Variant presentations of the exstrophy-epispadias complex (EEC) span a wide range of abnormalities. The rarity and diversity of EEC variants can lead to challenges in the diagnosis and subsequent management of this population., Methods: The authors reviewed an institutional database of 1336 EEC patients from 1975 to 2018 for variant presentations of EEC. Variant presentations included those with skin covered bladder exstrophy (BE), duplicate bladders, superior vesical fistula, and epispadias with major bladder prolapse. Surgical management and outcomes were assessed., Results: In total, 44 EEC variants were identified. Nineteen (43%) presented with a skin-covered BE variant. Five patients presented with duplicate BE, while 6 presented with superior vesical fistula. Fourteen patients (32%) presented with epispadias with major bladder prolapse. Overall, 36 (82%) EEC variants underwent primary bladder closure, at a median of 135 days after birth (range 1-2010), with 21 (58%) undergoing pelvic osteotomy. Primary closures were successful in 89% of cases. Continence procedures were performed in 17 patients. This includes 5 patients who underwent bladder augmentation. However even without a continence procedure, continence with volitional voiding was found in 8 patients., Conclusion: The most common EEC variant is the skin-covered form of BE. In order to expedite appropriate management, accurate diagnosis upon initial presentation is crucial. Still, successful surgical reconstruction often results in continence that is similar to, or better than, nonvariant EEC presentations., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To explore the use of concomitant bladder neck reconstruction (BNR) and creation of a continent stoma (CS) in patients who are not quite eligible for BNR but still strongly desire volitional voiding., Methods: The authors retrospectively reviewed an institutional database of patients with exstrophy-epispadias complex who underwent BNR-CS between 2000 and 2015. Indications for a BNR-CS, perioperative outcomes, and continence status were evaluated. Method of voiding and continence status were analyzed for patients with greater than 6 months of follow-up after the BNR-CS., Results: A total of 24 patients with exstrophy-epispadias complex (15 male and 9 female) underwent BNR-CS at a median age of 8.9 years (range 5.4-17.4). This included 18 patients with classic bladder exstrophy, 5 with epispadias, and 1 with a cloacal exstrophy variant. There were 5 surgical complications (20.1%) following the BNR-CS, including 3 febrile urinary tract infections, 1 superficial wound infection, and 1 urethrocutaneous fistula. The median follow-up time from the time of BNR-CS was 1.1 years (range 0.1-14.1). Seventeen of 24 patients (71%) had a follow-up greater than 6 months and were evaluated for continence. Twelve patients (71%) were completely dry for intervals greater than 3 hours following BNR-CS. Five (29%) did not achieve continence with BNR-CS. Of those 5 patients, 3 (60%) underwent subsequent bladder neck transection., Conclusion: Combined BNR and CS is a suitable alternative to achieve urinary continence in patients who are not ideal candidates for BNR alone. This approach can offer a select group of patients the opportunity for volitional voiding., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To evaluate human acellular dermis (HAD) as an adjunct during bladder neck transection (BNT) by comparing surgical outcomes with other types of tissue interposition., Methods: A prospectively maintained institutional database of exstrophy-epispadias complex (EEC) patients was reviewed for those who underwent a BNT with at least 6 months follow-up. The primary outcome was the occurrence of BNT-related fistulas., Results: In total, 147 EEC patients underwent a BNT with a mean follow-up time of 6.9 years (range 0.52-23.35 years). There were 124 (84.4%) classic exstrophy patients, 22 (15.0%) cloacal exstrophy patients, and 1 (0.7%) penopubic epispadias patient. A total of 12 (8.2%) BNTs resulted in fistulization, including 4 vesicoperineal fistulas, 7 vesicourethral fistulas, and 1 vesicovaginal fistula. There were 5 (22.7%) fistulas in the cloacal exstrophy cohort and 7 (5.6%) fistulas in the classic bladder exstrophy cohort (P = .019). Using either HAD or native tissue flaps resulted in a lower fistulization rate than using no interposed layers (5.8% vs 20.8%; P = .039). Of those with HAD, the use of a fibrin sealant did not decrease fistulization rates when compared to HAD alone (6.5% vs 8.8%, P = .695). There was no statistical difference in surgical complications between the use of HAD and native flaps (8.6% vs 5%, P = .716)., Conclusion: Use of soft tissue flaps and HAD is associated with decreased fistulization rates after BNT. HAD is a simple option and an effective adjunct that does not require harvesting of tissues in patients where a native flap is not feasible., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To explore the long-term outcomes and indications for cystectomy in patients with bladder exstrophy. Although rare, cystectomy is the final surgical alternative to bladder repair among these patients with a poor quality bladder template., Methods: A prospectively maintained database of 1298 patients with exstrophy-epispadias complex was reviewed for patients who underwent cystectomy between 1970 and 2015 at the authors' institution. Demographic data, indication for cystectomy, surgical history, postoperative outcomes, and continence status were collected., Results: Eighteen (6 male; 12 female) patients with exstrophy (15 classic bladder exstrophy; 2 bladder exstrophy variants; 1 cloacal exstrophy) underwent cystectomy at a median age of 3.8 years. Six patients (33.3%) underwent primary cystectomy without attempted bladder closure. Eight patients (44.4%) had a history of failed primary closure with loss of capacity or inadequate growth after closure. Four patients (22.2%) had successful primary closure but underwent cystectomy secondary to poor bladder compliance with declining renal function or poor bladder growth or quality. Urinary diversion included 6 cutaneous ureterostomies, 4 bowel conduits (1 ileal; 3 colon), 6 continent urinary diversions with ileosigmoid reservoir, and 1 ureterosigmoidostomy. Of 8 patients who underwent a continence procedure, all were dry at a median of 25.3 months after cystectomy., Conclusion: Cystectomy was most commonly indicated in intrinsically diseased bladder templates that remained too small despite permitting time for interval growth. These bladders often were of poor quality and compliance and did not reduce into the pelvis on examination. It was, however, possible to achieve urinary continence in these patients with cystectomy and urinary diversion., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To characterize the causes of re-augmentation in patients with classic bladder exstrophy (CBE)., Methods: A prospectively maintained institutional database of 1327 exstrophy-epispadias complex patients was reviewed for patients with CBE who underwent more than 1 augmentation cystoplasty (AC) procedure. Data regarding bladder capacities, complications following AC, and reasons for re-augmentation were evaluated., Results: A total of 166 patients with CBE underwent AC. Of these, 67 (40.4%) were included in the control group and 17 (10%) patients underwent a re-augmentation. There were several indications for re-augmentation including continued small bladder capacity (17 of 17), inadequate bladder necks (8 of 17), failed rattail augmentation (2 of 17), stomal incontinence (1 of 17), a urethrocutaneous fistula (1 of 17), and an hourglass augmentation (1 of 17). Of note, 5 of the 17 patients (29%) had a re-augmentation procedure with a ureteral reimplantation. The sigmoid colon was the most commonly used bowel segment in the failed initial AC (8 patients), whereas the ileum was the most commonly used segment during re-augmentation (12 patients). In the re-augmentation cohort, the mean amount of bowel used during the first AC procedure was 12 cm (standard deviation [SD] 3.6) compared with 19 cm (SD 5.0) during re-augmentation. The mean amount of bowel used for control group augmentations was 20.8 cm (SD 4). The mean re-augmentation preoperative bladder capacity of 100 mL (SD 60) immediately increased after re-augmentation to 180.8 mL (SD 56.4) (P = .0001)., Conclusion: Bladder re-augmentation is most commonly required in the setting of a small bladder capacity after an initial AC, when an insufficient amount of bowel is used during the first AC procedure., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the state of autophagy and its interactions with apoptosis and cell proliferation in patients who underwent successful early closure or delayed closure of exstrophy. They compared those outcomes with cell culture samples from patients with vesicoureteral reflux as control., Patients and Methods: Primary cultures of bladder smooth muscle cells (SMCs) were established from patients with successful neonatal bladder closure (group 1, N = 5), delayed closure because of small bladder template (group 2, N = 5), and vesicoureteral reflux as control (group 3, N = 5). The myogenicity of the cultures was determined using anti-Desmin antibody. Immunostainings for LC3 to assess autophagy and Ki67 to assess cell proliferation were applied. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick-end labeling assay., Results: Autophagy marker (LC3) expression was significantly higher in the delayed closure group than in the other groups, whereas no significant difference was noted between the neonatal closure and the control groups. Apoptotic indices of the SMCs were remarkably higher in SMC cultures from the delayed closures than in the neonatal closure and the control groups. A significantly lower expression of proliferation marker (Ki67) in the delayed closure group compared with the control and the neonatal closure group was also of note., Conclusion: Patients with small bladder template and delayed closure showed upregulated autophagic process and increased apoptotic indices while experiencing a dramatic decrease in the proliferation of their bladder SMCs. Finally, the concept of manipulating autophagy may lead to promising outcomes for patients with bladder exstrophy in the future., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate corporal tissue viability and changes in endothelial content following current techniques used for epispadias repair in an animal model., Materials and Methods: Sixty rabbits were allocated into 3 groups: sham operation (penile degloving), complete disassembly model, and Cantwell-Ransley model. On weeks 2, 4, 12, and 24 postoperation, the penile tissue was harvested and processed for (1) Masson's trichrome staining for smooth muscle cell (SMC)-to-collagen ratios, (2) immunohistochemical staining for endothelial factor (CD31), and transforming growth factor beta 1 (TGF-β1) (3) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) assay to detect apoptosis., Results: Masson trichrome staining of corporal tissue showed significant decrease in SMC-to-collagen ratio in complete disassembly group compared with sham operation group. The expression of CD31 was significantly lower (P <.05) in complete disassembly group compared with the other groups at all time points, whereas no significant difference was observed between the Cantwell-Ransley group and the sham operation group. Moreover, apoptotic index was markedly higher in the complete disassembly group compared with the 2 other operation groups (P <.05). Immunohistochemistry also showed a significantly higher expression of TGF-β1 in the penile tissue after complete disassembly than Cantwell-Ransley or sham operation., Conclusion: Complete detachment of the urethra from the corpus cavernosa may result in endothelial dysfunction, alteration of SMC content of erectile tissue, and replacement of the native cavernosal tissue with fibrotic tissue. An increased expression of TGF-β1, following the complete disassembly technique, might be one of the important factors causing the abovementioned alterations., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the surgical course for treating bladder polyps in patients with exstrophy epispadias complex (EEC). EEC bladder polyps are unique pathologic entities, with a distinct difference between polyps discovered at birth and polyps developed after failed exstrophy closure., Methods: A prospectively maintained database of 1300 patients with EEC was reviewed for bladder exstrophy patients with bladder polyps. The following data were obtained: patient demographics, polyp type, past medical and surgical history, and continence outcomes. Polyps were categorized as (1) primary, bladder polyps at birth or during neonatal period; and (2) secondary, bladder polyps following a failed exstrophy closure., Results: Of 1300 EEC patients, 43 patients with polyps met the inclusion criteria. All closures for primary polyp patients were successful, and continence outcomes remained similar in early and delayed closures (P = .689). Secondary polyp patients were more likely to require augmentation to increase bladder capacity (P = .033). Bladder neck reconstruction (n = 8) was successful in 83.0% of patients with primary polyps, and none were successful for those with secondary polyps (P = .035)., Conclusion: Delaying primary bladder closure for patients with small polypoid bladder templates did not affect closure or continence outcomes. However, primary and secondary polyps may require different surgical interventions. Bladder neck reconstruction was markedly less successful in secondary polyp patients, and secondary polyp patients were more likely to need augmentation to increase bladder capacity. This study emphasizes the importance of a successful primary closure and suggests that secondary polyps are an indicator of decreasing potential for bladder growth., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To provide sexual function and quality of life outcomes in patients with severe penile deficiency who underwent radial forearm flap phalloplasty with and without penile prosthesis implantation., Patients and Methods: Patients with history of severe penile deficiency who underwent microsurgical radial forearm flap phalloplasty with and without penile prosthesis implantation between 2007 and 2014 were identified. They completed a set of web-based validated questionnaires including the International Index of Erectile Function, the Pediatric Penile Perception Score, the Sexual Quality of Life for Men, and several items addressing general quality of life. Outcomes were compared between groups., Results: Nine of the 12 identified patients who had prosthesis after phalloplasty and 4 out of the 7 phalloplasty-only patients completed the survey, resulting in an overall response rate of 68%. Among the phalloplasty-prosthesis patients, 66% reported current sexual activity and 78% reported regular masturbation, whereas 1 of the 4 phalloplasty-only patients reported both. Prosthesis patients scored notably higher in all domains of the International Index of Erectile Function except for sexual desire. In contrast, they demonstrated similar scores of penile perception, as well as general and sexual quality of life., Conclusion: Among patients who have undergone flap phalloplasty, the subsequent placement of penile prosthesis appears to effectively allow for both intercourse and masturbation, resulting in measurable improvements in orgasmic function, intercourse satisfaction, and overall sexual satisfaction. Despite these important benefits, prosthesis placement does not appear to result in improvements in penile perception scores, or general or sexual quality of life., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Study Objective: To characterize Müllerian anatomy in 46,XX cloacal exstrophy patients., Design: Retrospective review of prospectively maintained, institutionally approved exstrophy-epispadias-cloacal exstrophy database., Setting: Tertiary care, high-volume exstrophy center (Division of Pediatric Urology, The Johns Hopkins Hospital, Baltimore, Maryland)., Participants: We included 31 patients who were genetically female with cloacal exstrophy for whom records included detailed evaluation of Müllerian anatomy., Interventions: None., Main Outcome Measures: Müllerian structures, method of evaluation, management, and sexual activity., Results: Of our patients, 12.9% (3/31) had no identified abnormalities. Vaginal anatomy was described for 30 patients; 3/30 had vaginal agenesis, 14/30 had a single vagina, and 13/30 had vaginal duplication. Of 14 patients with 1 vagina, 5 had atresia/hypoplasia, and 1 had a lateral displacement. One patient with 2 vaginas also had distal atresia. Of the cervices evaluated, 9/14 were duplicated (2/9 with a solitary vagina), and 19/27 of the uteri were duplicated (6/22 with 1 vagina, 1/22 with no vagina). Five patients required imaging to fully characterize their anatomy, and 7 patients had studies that failed to identify Müllerian structures seen in the operating room or on physical examination. Common reconstructive surgeries included vaginoplasties, incisions of vaginal septa, colporrhaphies, and hysterectomies. Sexual activity was confirmed for 3 patients, 2 of whom had conceived., Conclusion: Most female cloacal exstrophy patients exhibit abnormalities of the Müllerian system. Axial imaging and ultrasound are helpful diagnostic adjuncts but do not replace careful physical examination and assessment in the operating room. Further studies of sexual activity and fertility are warranted., (Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Bladder exstrophy is a rare major birth defect which requires specialized surgical care. Associated genitourinary tract anomalies are extremely rare in this population, yet significantly impact surgical planning and outcomes. In this case, a full-term newborn girl with a prenatal diagnosis of classic bladder exstrophy was found to have a complete duplicated left collecting system with an ectopic ureter inserted to urethral plate. The patient underwent modern staged repair of exstrophy with bilateral anterior innominate osteotomies and concomitant ureteral reimplantation-the first reported case of ureteral reimplantation at the time of initial closure in a newborn., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To report our preliminary institutional experience of incorporating a tunica vaginalis flap (TVF) as an adjunct into primary or secondary epispadias repair., Patients and Methods: A prospectively maintained institutionally approved database of exstrophy-epispadias complex patients was used to identify and retrospectively review male patients who underwent epispadias repair from September 2010 to October 2014 at the authors' institution. Patients who underwent epispadias repair with TVF were identified and their clinical outcomes were measured., Results: A total of 49 male patients were identified as meeting inclusion criteria, of which 15 (2 isolated epispadias, 13 classic bladder exstrophy) underwent epispadias repair incorporating a TVF. Median age at time of repair was 12 months (interquartile range [IQR] 10-15.5). A median of 4 layers (IQR 4-5) was incorporated into each repair closure, applying EVICEL Fibrin Sealant as an additional layer in all patients. All patients received preoperative testosterone injection therapy of 2 mg/kg 5 and 2 weeks before surgery for penile growth. There were no intraoperative complications. Median follow-up of 19 months (IQR 12-23) revealed 5 patients who underwent epispadias revision, 3 (20%) of which developed a urethrocutaneous fistula. All patients had a successful repair without recurrence., Conclusion: The authors have found the utilization of a TVF with epispadias repairs to be beneficial but no better than the repair with our routine soft-tissue coverage in primary epispadias repair. However, in patients presenting with complex anatomy and limited tissue reserves, a TVF is an important adjunct to epispadias repair and/or revision and may lead to improved outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To analyze the outcomes of failed classic bladder exstrophy (CBE) reclosure with and without pelvic osteotomy. Each failed CBE closure decreases the chance of eventual continence. To minimize secondary failures, most institutions use pelvic osteotomy with reclosure. Reclosure with and without osteotomy can still fail., Methods: An institutional database of 1210 exstrophy-epispadias complex patients was reviewed for CBE patients who had 2 prior failed closures with the third closure at the authors' institution. Patient demographics, closure history, diastasis distance, bladder capacity, and outcomes were examined by chi-square tests comparing osteotomy status with first reclosure., Results: Of 848 CBE patients, 17 met inclusion criteria: 12 with osteotomy at reclosure (group 1) and 5 without (group 2). Median time between initial closure and reclosure in the 2 groups were 6.5 months (range, 0-42 months) and 3 months (range, 0-59 months), respectively. There was no significant difference in the rate of attaining sufficient bladder capacity for bladder neck reconstruction (BNR; 100 cc) between groups 1 and 2 (42% vs 40%; P = .490). Within group 1, patients receiving proper immobilization with external fixation (n = 5) demonstrated a significantly greater rate of attaining sufficient bladder capacity for BNR compared with patients who did not (80% vs 14%; P = .023). There were no differences in the rates of attaining dryness per urethra., Conclusion: CBE outcomes worsen with each successive failed closure. Reclosure should be performed with osteotomy and proper immobilization to maximize the chance of sufficient capacity for BNR or augmentation cystoplasty., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate a single referral center's experience with vesicoureteral reflux (VUR) and its role in management before bladder neck reconstruction (BNR) in exstrophy patients after modern staged repair of exstrophy (MSRE). VUR after primary closure of bladder exstrophy can usually be managed conservatively until ureteral reimplantation (UR) at the time of BNR. However, VUR in these patients is occasionally associated with febrile urinary tract infection and worsening renal function necessitating UR before BNR., Materials and Methods: A total of 199 patients who underwent MSRE were identified from an institutional review board-approved database. Patient demographics, closure history, postprimary closure VUR, history of urinary tract infection, cystography outcomes, renal function, history of UR before BNR, and UR outcomes were recorded. Univariate and multivariate analyses were performed to determine factors predicting high-grade VUR and the need for pre-BNR UR., Results: After primary closure, VUR was observed in 150 patients (75.4%) of whom 31 (15.58%) had high-grade VUR. Closure without osteotomy and postclosure outlet obstruction were independently associated with postprimary closure high-grade VUR (P <.05). Twenty-two patients (11.06%) required pre-BNR UR. Female gender and those with high-grade VUR were more likely to require UR before BNR (P <.05). Early UR did not affect the continence rate., Conclusion: VUR after exstrophy closure can generally be managed with conservative treatment and periodic monitoring of the upper urinary tracts. About 11% of patients undergoing MSRE will require UR before BNR. Closure without osteotomy and patients who develop outlet obstruction after closure are at increased risk for developing high-grade VUR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The clinical presentations of 17β hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency, 5α-reductase type 2 deficiency, and complete androgen insensitivity syndrome can be similar. However, those with 17β-HSD3 deficiency and 5α-reductase type 2 deficiency will develop virilization and should undergo gonadectomy after genetic testing before the age of puberty if reared in the female sex. Two sisters were initially diagnosed with complete androgen insensitivity syndrome as young children after testes were discovered during hernia surgery. Virilization occurred in both sisters during puberty, and a diagnosis of 17β-HSD3 deficiency was suspected. Confirmatory diagnosis through gene sequencing identified a heterozygous mutation for both a known splicing mutation and a previously unreported amplification mutation of the HSD17B3 gene., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate indications and applicability of continent and incontinent urinary diversion (CUD and IUD, respectively) in early childhood in patients with classic bladder exstrophy (CBE)., Methods: Using an institutionally approved exstrophy database, patients with CBE born after 1980 who underwent CUD or IUD by 2 surgeons within the first 5 years of life were identified. All aspects of their care and clinical outcomes were studied., Results: In the CUD group (n = 14), only 21% had successful primary closure. Indications were desire to be dry (7), persistent hydronephrosis (4), urinary tract infections (UTIs) (1), repeat CUD (1), and inaccessible proper follow-up (1). Three patients had neobladder creation, 10 had bladder augmentation with continent stomas, and 2 underwent ureterosigmoidostomy. Currently, all patients are dry with clean intermittent catheterization (CIC). In the IUD group (n = 5), only 1 had successful primary closure. In addition to small, noncontractile bladders, the indications for IUD were severe hydronephrosis (2), recurrent UTIs (2), and noncompliance with catheterization (1). Four patients were re-diverted to CUD after a mean of 9.4 years and 1 has colon conduit. All are socially dry via catheterization. There was no case of renal function loss or malignant transformation., Conclusion: The need for early diversion in CBE is primarily driven by upper tract changes after secondary closure and social factors. Urinary diversion can be safe in younger children with a favorable continence outcome., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To present the critical features of our postoperative plan for children undergoing delayed primary bladder closure because appropriate postoperative management is crucial to successful exstrophy repair., Methods: Using an institutionally approved database, patients with bladder exstrophy whose primary bladder closure was performed at least 1 month after birth were identified. All aspects of the postoperative management were reviewed., Results: A total of 20 patients (18 boys) were identified: 19 with classic bladder extrosphy and 1 with an exstrophy variant. The patients underwent closure at a mean age of 9.9 months. All patients underwent pelvic osteotomy and immobilization for an average of 34.8 days. Analgesia was administered by way of a tunneled epidural catheter in 90% of patients for an average of 18.8 days, and 12 patients (60%) required adjunct intravenous analgesia. Bilateral ureteral catheters and suprapubic tubes were used in all patients. Total parenteral nutrition was administered to 10 (83%) of 12 patients who underwent closure after 2000. All patients received preoperative antibiotics and 2 weeks of postoperative intravenous antibiotics that was followed by oral prophylaxis. The mean hospital stay was 6.3 weeks. With an average follow-up of 7.4 years, delayed closure was 100% successful., Conclusion: Successful delayed primary closure of bladder exstrophy requires a multidisciplinary approach. The keys to success include osteotomy, pelvic immobilization, analgesia, nutritional support, maximal bladder drainage, and infection prophylaxis., (Copyright © 2012. Published by Elsevier Inc.)

Objective: To determine the proportion and type of renal anomalies that occur in children born with classic bladder exstrophy., Material and Methods: All patients in a database of 1044 patients with the bladder exstrophy-epispadias-cloacal exstrophy complex were reviewed. Those with classic bladder exstrophy had their complete medical records reviewed and children with radiographic evidence of congenital renal anomalies were identified and characterized., Results: A total of 674 patients were identified with classic bladder exstrophy, of whom 462 had renal ultrasounds at the authors' institution. In this population, 13/462 (2.8%) had concomitant renal anomalies. The most common malformation was a duplicated collecting system in 6 patients. Hypoplastic or absent kidneys were present in 3 patients, pelvic kidney in 2, ureteropelvic junction obstruction in 1, and multicystic dysplastic kidney in 1 patient., Conclusion: Isolated renal anomalies occur at a rate of 2.8% in children born with classic bladder exstrophy. Although uncommon in this rare birth defect, anatomic understanding of the entire genitourinary system is critical for operative planning and long-term follow-up of patients with bladder exstrophy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

An infant born at 38-weeks' gestation presented with ambiguous genitalia. Cytogenetic evaluation revealed an uncommon 45,X/46,X,idic(Y) mosaic karyotype. Pelvic ultrasonography, genitogram, and magnetic resonance imaging confirmed a long common urogenital sinus, vagina, cervix, unicornuate uterus, phallus, and bilateral intra-abdominal gonads resembling testes. The parents chose a male sex of rearing, and the infant underwent total abdominal hysterectomy, vaginectomy, bilateral gonadectomy, and first-stage hypospadias repair at 19 months of age. The histopathologic findings were consistent with ovotesticular disorder of sex development with a unique combination of testis and ovary on the left and testis and streak gonad on the right., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To characterize the relationship between pediatric kidney stone disease and the presence of hypertension (HTN), diabetes mellitus (DM), and obesity. In adults, kidney stone disease has been associated with medical comorbidities such as HTN, DM, and obesity. Similar analyses have never been performed for the pediatric population., Methods: The 2003 and 2006 Kids' Inpatient Databases were queried to identify subjects treated for kidney stone disease ("International Classification of Diseases" codes 9592.0 and 592.1). The comorbidities of HTN, DM, and obesity were identified using the provided comorbidity software. The risk of kidney stone disease associated with age, sex, and comorbidity status was evaluated using multivariate logistic regression., Results: A total of 6,115,443 subjects were evaluated. Of these, 14,245 (0.2%) had a diagnosis of upper tract calculus (4092 boys and 10,045 girls, sex unavailable for 108). Age was the strongest independent predictor of stone risk (P < .0001). HTN was associated with a significantly increased risk of stone diagnosis in children ≤10 years old and DM for children ≤5 years old. Stone risk was not affected by obesity in any age group., Conclusions: The results of our study have shown that kidney stone disease is significantly associated with age among all children and both HTN and DM for young children. Although exploratory, these findings are novel and suggest that kidney stone disease among young children might be associated with nonrenal, systemic disease states., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To define the sex prevalence of inpatient hospital discharges for pediatric patients diagnosed with upper urinary tract stone disease., Methods: The study examined inpatient admissions for pediatric urolithiasis in 2003, using the Healthcare Cost and Utilization Project Kids' Inpatient Database. We used the International Classification of Disease, 9th edition, Clinical Modification codes, to identify patients with a principal diagnosis of renal (592.0) or ureteral (592.1) calculi. Sex prevalence was assessed, and the results were stratified by age group., Results: In the 2003 Kids' Inpatient Database, the sex distribution among pediatric patients with stone formation varied significantly by age. In the first decade of age, a male predominance was found that had shifted to a female predominance in the second decade. Overall, however, girls in the pediatric population were more commonly affected by stones than were boys., Conclusions: In this nationally representative sample, the sex distribution of pediatric urolithiasis varied with age, with boys more commonly affected in the first decade of age and girls in the second decade. Although the reason for this unique epidemiologic finding is not readily apparent, additional studies can build on this hypothesis-generating work.

Objectives: With modern reconstructive surgical techniques and better neonatal intensive care unit care, patients with the bladder exstrophy-epispadias complex are now living much longer than they did previously. As these patients age, the men will begin to seek out adult urologists for common conditions such as benign prostatic hyperplasia and prostate cancer screening. We present the first known man with the exstrophy-epispadias complex to be diagnosed with prostate cancer., Methods: After obtaining institutional review board approval, the computerized charting system at our institution was used to review this patient's medical record. A computerized literature search was then conducted using PubMed to confirm that no other cases of prostate cancer had been reported in the exstrophy-epispadias population., Results: The patient underwent radical retropubic prostatectomy by an adult urologic oncologist assisted by a pediatric urologist with expertise in bladder exstrophy. The patient later required cystectomy and ileal conduit for disease at the bladder neck, as well as external beam radiotherapy and androgen deprivation therapy. During 1 year of follow-up, his prostate-specific antigen level was undetectable., Conclusions: We have described the first case of prostate cancer in the exstrophy-epispadias population, proving that these patients are at risk and that radical retropubic prostatectomy is a viable treatment option. Practicing adult urologists will need to be aware of this patient population, because they will be seeking out care for common urologic issues as they age. Special considerations of the diagnosis, management, and treatment of prostate cancer in this patient population are discussed.

Recurrent urogynecologic complications in women with bladder exstrophy are common and complex given the congenital abnormalities of the bony, connective tissue, and muscular support of the pelvic floor, as well as the length and axis of the vagina. Management of these issues is challenging and often requires unique surgical strategies. We present the case of a distinct, individualized surgical approach to management of several complicated urogynecologic issues in a woman with bladder exstrophy who desired surgical correction of a non-healing fistula, pelvic organ prolapse, and a short vagina.

The authors report a rare variant of the exstrophy-epispadias complex in which the patient has two bladders and complete duplication of müllerian structures. We also discuss the treatment of the patient's orthopedic and genitourinary conditions. The patient's prognosis is excellent, and she is expected to be fully continent, able to void spontaneously, and conceive children.

Objectives: To evaluate the hypothesis that anxiety disorders are common comorbid conditions in children with the epispadias-exstrophy complex., Methods: Twenty consecutive outpatient exstrophy subjects ranging in age from 5 to 22 years were assessed using a formalized semistructured psychiatric evaluation and were categorized according to the Diagnostic and Statistical Manual of Mental Disorders, version IV, criteria. Disorders were identified if subjects endured moderate to severe impairment in their home, academic, and social environments., Results: All 20 subjects met the criteria for at least one anxiety disorder; 19 met criteria for more than one anxiety disorder. The adolescent subjects described a gradual waning of some specific symptoms some time after surgical correction of the physical conditions (eg, incontinence) but intensifying sexual anxiety with age., Conclusions: The epispadias-exstrophy complex appears to be associated with clinically significant vulnerabilities for anxiety disorders in children.

Objectives: To evaluate the affinity between human stem cells and human bladder cells by analyzing their migration and proliferation patterns in co-culture. Human stem cells have great potential for tissue engineering purposes. Co-culture of stem cells with mature cells may promote differentiation., Methods: Equal numbers of green fluorescent protein-labeled human embryonic germ cell derivates (SDECs) were plated, either alone or in the presence of red fluorescence-labeled (PKH 26) human bladder smooth muscle cells (SMCs) or urothelial cells (UROs). The co-cultures shared the same media (EGM2MV). The migration patterns of the different cell lines were measured daily, using an integrated grid, for 8 days with fluorescence microscopy., Results: SDECs, grown alone, had a robust basal migration rate of between 0.3 and 0.7 mm/day compared with SMCs, which had a rate of 0.1 to 0.3 mm/day and UROs with a rate of 0.1 to 0.2 mm/day. Stem cell migration was enhanced in co-culture with SMCs or UROs to 0.5 to 1.0 mm/day. Migration of SDECs was more linear, directed toward SMCs or UROs, compared with the circumferential growth when plated alone. SMCs, more than UROs, migrated more rapidly in the presence of stem cells., Conclusions: Human stem cells showed improved migration in the presence of mature human bladder cells and were attracted to them, as shown by the altered direction of growth. Thus, co-culture of human stem cells with host SMCs can enhance seeding of matrices due to positive chemotaxis. Identifying the responsible factors may help to augment chemotaxis between desired cell types and optimize tissue regeneration.